Effect of selective inhibition of soluble guanylyl cyclase on the K(Ca) channel activity in coronary artery smooth muscle.
Activation of a soluble guanylyl cyclase plays an important role in nitric oxide (NO)-induced vasodilation. Recently, we have reported that NO increases the calcium-activated potassium (K(Ca)) channel activity in vascular smooth muscle cells from coronary arteries. The present study examined the role of the soluble guanylyl cyclase in the control of basal activity of the K(Ca) channels and in mediating NO-induced activation of the K(Ca) channels in vascular smooth muscle cells, using a selective inhibitor of this enzyme, 1H-[1,2,4]oxadiazolo[4,2-alpha]quinoxalin-1-one (ODQ). In the cell-attached patch-clamp mode, addition of ODQ into the bath solution (10 micromol/L) decreased the K(Ca) channel activity by 59% and attenuated activation of the channels induced by the NO donor, deta nonoate, by 70%. ODQ had no effect on 8-bromo-cGMP-induced activation of the K(Ca) channels. Deta nonoate produced a concentration-dependent relaxation of precontracted coronary arteries. When ODQ was added to the bath, the deta nonoate-induced relaxations were inhibited. The IC50 for deta nonoate was decreased by about 25-fold and the maximal effect of deta nonoate was reduced by about 60%. A specific K(Ca) channel inhibitor, iberiotoxin, decreased deta nonoate-induced vasodilation but to a lesser extent than ODQ. However, ODQ was without effect on the vasodilation induced by a prostacyclin analog, iloprost, and by adenosine. These results indicate that a soluble guanylyl cyclase and cGMP play an important role in the control of the K(Ca) channel activity in coronary arterial smooth muscle cells. K(Ca) channel activation participates in the NO-induced vasodilation in coronary circulation.
Li
P L
PL
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226, USA. pli@post.its.mcw.edu
Jin
M W
MW
Campbell
W B
WB
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D016285:Iloprost / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009603:Nitroso Compounds / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology*; D012604:Scorpion Venoms / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D009603:Nitroso Compounds; D010069:Oxadiazoles; D010455:Peptides; D015221:Potassium Channels; D011810:Quinoxalines; D012604:Scorpion Venoms; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; C016276:8-bromocyclic GMP; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C064719:iberiotoxin; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D016285:Iloprost; D000241:Adenosine